6Can we stop progression of ankylosing spondylitis?
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of unknown origin affecting the axial skeleton including the sacroiliac (SI) joints and the spine and also the peripheral joints and the entheses [1]. Since AS usually starts in the third decade, it affects people for most of their life. AS has a strong genetic component, with HLA-B27 being the most relevant gene. Clinically, pain and stiffness in the back are the leading complaints. In addition, the patient may suffer from peripheral joint pain or enthesitis, typically of the heel, or from bouts of uveitis. With time, bony ankylosis of the SI joints and the spine develops in many patients. Bony ankylosis at the spine may affect the vertebral bodies (syndesmophyte formation) as well as the facet, the zygapophyseal and the costovertebral joints. It is particularly spinal ankylosis, which results in loss of spinal mobility and changes in posture such as the development of thoracic kyphosis and irreversible stiffness. In a large proportion of patients, the disease course in AS that runs is fluctuating with not only periods of flares but also periods of remission or low disease activity. Some patients, however, suffer from persistently high disease activity.
Section snippets
Excessive bone apposition in AS
Bony overgrowth in AS has traditionally been considered as a structural damage arising from chronic immune activation and inflammation. In contrast to rheumatoid arthritis, where structural changes are of primarily catabolic nature, resulting in a net loss of bone substance in the vicinity of joints, structural changes in AS are dominated by anabolic processes. Bony spur formation, which arises from the cortical bone surface, is a common feature of AS and virtually affects all skeletal
Cellular and molecular mechanisms of bone formation in AS
A better insight into the molecular regulation of new bone formation is key for defining the optimal intervention strategies to retard or block bony ankylosis in patients with AS. Ankylosis in AS is based on the apposition of new bone along periosteal skeletal sites requiring differentiation of osteoblasts, which are the bone-forming cells. Osteoblasts develop from mesenchymal cell precursor cells, which cover the inactive periosteal bone surface. Growth as well as injury, such as observed
Acknowledgements
GS' work is supported by the Deutsche Forschungsgemeinschaft DFG (SFB643, SPP1468, FOR661), the Bundesministerium für Forschung und Bildung BMBF (project ANKYLOSS), the European Union projects Masterswitch, Kinacept and Adipoa, the Interdisziplinäres Zentrum für Klinische Forschung Erlangen and the Spondyloarthritis Immunology Reserach Alliance (SpIRAL).
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Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures
2015, Translational ResearchCitation Excerpt :The mechanisms leading to bone formation and progression of SpA are still not well defined.8 Lories et al have suggested that inflammation and bone anabolic response, leading to ankylosing, are maintained in parallel,9 whereas Schett et al rather suggested that inflammation gradually decreases until active repair process is initiated, leading to ankylosis.10 Formation of bony spurs at the enthesis may occur by a process resembling endochondral ossification.11
Functional mechanism of miR-92b-3p in osteogenic differentiation of fibroblasts in patients with ankylosing spondylitis via the TOB1/BMP/Smad pathway
2023, Journal of Orthopaedic Surgery and ResearchCD_99 G1 neutrophils modulate osteogenic differentiation of mesenchymal stem cells in the pathological process of ankylosing spondylitis
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